The mechanisms which control the level of responsiveness of infected hosts to Trypanosoma cruzi are not well understood. The study of immunoregulation of parasite-specific responses has been difficult due primarily to the lack of appropriate assay systems to measure in vitro immune responses to parasites or their antigens. The purpose of the research proposed is to refine recently developed assay systems and to develop new assays which will permit the measurement of in vitro responses to T. cruzi. These assays include the induction and measurement of antibody production by spleen cells from normal and T. Cruzi-infected mice to TNP-T. cruzi and T. cruzi (non-haptenated) and of proliferative responses of long-term T. cruzi-specific T. cells. With the use of these assays, the role of various regulatory mechanisms will be examined for the ability to directly control the expression of parasite-specific immune responsiveness. In addition, measurement of in vitro antibody responses to parasite antigens will provide the means to determine if the presence of nonspecific immunosuppression in T. cruzi infected hosts make these hosts less capable of responding to T. cruzi and/or if parasite-specific suppressor mechanisms exist. Corollary in vivo studies are also planned to determine if the regulatory pathways described in vitro also function in vivo. The role of lymphokine and monokine production in susceptibility or resistance to T. cruzi will also be examined. Lastly, the in vitro assays for measuring the response to T. cruzi will be utilized to study the antigens on T. cruzi which are immunogenic in vitro. The development of means for inducing immunity to infection with T. cruzi clearly depends on first elucidating how the response to the parasite is regulated. Completion of the work propose in this application will determine this and will also provide some information on what antigens are important in induction of immunity to T. cruzi. This information will be helpful in developing a long-term strategy for treatment and eradication of Chagas' disease.